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The effect of Gemcitabine chemotherapy on lung intertiatial macrophages (IMs) from tumor-free mice

ABSTRACT: Chemotherapy offers long-term clinical benefits to many cancer patients. However, several pre-clinical studies have demonstrated that certain cytotoxic drugs enhance metastasis via multiple mechanisms. These studies have mainly focused on tumor cell-derived inflammation. The importance of host responses triggered by chemotherapy in regulating cancer metastasis has not been fully explored. Our recent studies have showed that multi-dose Gemcitabine (GEM) treatment promoted breast cancer lung metastasis in a transgenic spontaneous breast cancer animal model. Both CCR2+ macrophages and monocytes were increased in the lungs of GEM-treated mice. Further, the increase of CCR2+ macrophages and monocytes were observed in naïve (tumor-free) mice after GEM treatment. These changes were largely caused by chemotherapy-induced reactive myelopoiesis that are biased toward monocyte development. Importantly, the host responses following chemotherapy promote tumor metastasis, which is dependent on CCL2/CCR2 axis. To understand how lung macrophages contribute to the pro-metastatic effect of chemotherapy, the expression profile of lung interstitial macrophages (IMs) from GEM treated and PBS control tumor-free mice was examined.

ORGANISM(S): Mus musculus

PROVIDER: GSE217105 | GEO | 2023/03/22

REPOSITORIES: GEO

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